The rational for this proposed research is that risk estimates for lung cancer due to radon are based on an extrapolation of data from underground miners who breathed high concentrations of the radioactive gas, corresponding to multiple alpha-particle traversals of the basal cells of the bronchial epithelium. On the other hand, in a domestic situation, it is likely that the most relevant LET range to study for radon effect sis between 150 and 220 keV/um. With the availability of the single particle beam at the Radiological Research Accelerator Facility, this currently-funded project can be expanded to examine the mutagenic potential of a defined number of alpha particle traversal at the S1 locus of human hamster hybrid (AL) cells. Specifically, the mutagenic yield induced by defined number of alpha traversals will be compared with that from an equivalent mean number of particle traversals, the latter being measured on the tract segment facility In addition, the mode of interaction in mutation induction for single particle traversal with other environmental pollutant, such as tobacco smoke, indicated from epidemiological studies as compounding factors in the induction of lung cancers from miners will also be investigated. This proposed study will address the long sought-after question of whether a single alpha particle traversal is indeed mutagenic. Another exciting area of study where the single particle beam will be of tremendous value is in the assessment of mutagenicity from radon alpha particles in combination with other environmental carcinogens known to be confounding factors for lung cancer development among underground miners, particularly tobacco smoke condensate. Results of these studies Will facilitate the extrapolation from high to low does in the presence of confounding factors under systematic and well-controlled conditions. Once the S1 mutants are isolated, we will compare the molecular spectrum between mutants induced by single versus mean particle traversals. The availability of primer sequences for several human chromosome 11 marker genes makes possible the use of multiplex PCR to evaluate the deletion pattern from S1-mutants using small quantities of DNA.